Search

Background: This manuscript describes modifications to a pencil beam scanning (PBS) proton gantry that enables ultra-high dose rates (UHDR) irradiation, including treatment planning and validation., Methods: Beamline modifications consisted of opening the energy slits and setting the degrader to pass-through mode to maximize the dose rate. A range shifter was inserted upstream from the isocenter to enlarge the spot size and make it rotationally symmetric. We measured the beamline transport efficiency and investigated the variation in output due to the recombination of charge in the dose monitoring chamber. The output calibration was performed through a parallel plate chamber (PPC05), and an intercomparison was performed for various detectors. The pre-clinical field for mice irradiation consisted of different dose levels to deliver uniform doses in transmission mode. The field dose rates were determined through log files while scripting in TPS was used to estimate PBS dose rates. The survival experiments consisted of irradiating the full pelvis of the mice at UHDR and conventional dose rates., Results: The spot size was constant with beam current and had a sigma of 8.5 mm at the isocenter. The beam output increased by 35% at 720 nA compared to 5.6 nA, primarily due to recombination in the dose-monitoring ion chambers. The Faraday Cup and PPC05 agreed within 2%, while other detectors were within 3% of FC for dose rates <60 Gy/s. The pre-clinical fields' PBS dose rate is above 45 Gy/sec for all voxels within the target volume. The average and PBS dose rates decrease as field size increases and approaches 40 Gy/s for a field size of 7x7 cm 2 . All UHDR arms showed better survival than the corresponding conventional dose rate arms., Conclusions: We successfully modified a clinical system to perform UHDR pre-clinical experiments. As part of our pre-clinical experiments, we observed the FLASH effect concerning mice survival., Competing Interests: SR was employed by company Ion Beam Applications. VG was employed by company Ion Beam Applications. JM: Research funding from the Germany Academic Exchange Service. RR: Consulting fees from AstraZeneca, Gilead Sciences, IBA. Food/beverages from Elekta, Siemens, Viewray. JZ: Research funding and consulting/honoraria fees from AstraZeneca, Gilead Sciences, IBA. Research funding from NIH RCA258997A and Kuni Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Ion Beam Applications. The funder had the following involvement in the study: advising for study design, analysis and interpretation of collected data, writing off of this article., (Copyright © 2024 Saini, Erickson, Vander Stappen, Ruth, Cui, Gorman, Rossomme, Cao, Ford, Meyer, Bloch, Wong, Grassberger, Rengan, Zeng and Schwarz.)

Purpose: Animal studies with ultrahigh dose-rate radiation therapy (FLASH, >40 Gy/s) preferentially spare normal tissues without sacrificing antitumor efficacy compared with conventional dose-rate radiation therapy (CONV). At the University of Washington, we developed a cyclotron-generated preclinical scattered proton beam with FLASH dose rates. We present the technical details of our FLASH radiation system and preliminary biologic results from whole pelvis radiation., Methods and Materials: A Scanditronix MC50 compact cyclotron beamline has been modified to produce a 48.7 MeV proton beam at dose rates between 0.1 and 150 Gy/s. The system produces a 6 cm diameter scattered proton beam (flat to ± 3%) at the target location. Female C57BL/6 mice 5 to 6 weeks old were used for all experiments. To study normal tissue effects in the distal colon, mice were irradiated using the entrance region of the proton beam to the whole pelvis, 18.5 Gy at different dose rates: control, CONV (0.6-1 Gy/s) and FLASH (50-80 Gy/s). Survival was monitored daily and EdU (5-ethynyl-2´-deoxyuridine) staining was performed at 24- and 96-hours postradiation. Cleaved caspase-3 staining was performed 24-hours postradiation. To study tumor control, allograft B16F10 tumors were implanted in the right flank and received 18 Gy CONV or FLASH proton radiation. Tumor growth and survival were monitored., Results: After 18.5 Gy whole pelvis radiation, survival was 100% in the control group, 0% in the CONV group, and 44% in the FLASH group ( P < .01). EdU staining showed cell proliferation was significantly higher in the FLASH versus CONV group at both 24-hours and 96-hours postradiation in the distal colon, although both radiation groups showed decreased proliferation compared with controls ( P < .05). Lower cleaved caspase-3 staining was seen in the FLASH versus conventional group postradiation ( P < .05). Comparable flank tumor control was observed in the CONV and FLASH groups., Conclusions: We present our preclinical FLASH proton radiation system and biologic results showing improved survival after whole pelvis radiation, with equivalent tumor control., Competing Interests: Juergen Meyer receives research funding from the Germany Academic Exchange Service. Ramesh Rengan receives consulting fees from AstraZeneca, Gilead Sciences, IBA. Food/beverages from Elekta, Siemens, ViewRay. Jing Zeng receives research funding and consulting/honoraria fees from AstraZeneca, Gilead Sciences, IBA, Research funding from NIH RCA258997A and Kuni Foundation. All other authors have no disclosures., (© 2023 The Author(s).)